Brain-Behavior Markers of Negative Affectivity, Comorbidity in Anxiety Disorders

 描述(由申请人提供)：焦虑症(ADS)在神经功能障碍方面可能更相似而不是不同。检查独立于特定诊断的表型变异可能有助于阐明ADS中精神病理学的基本生物行为基础，从而改进分类和治疗。例如，ADS中的共病很常见，已知与严重程度和情绪反应的衡量标准有关，如自我报告的负面情感(NA)，但其潜在的神经生物学证据很少。这个 K23的主要目标是为应聘者提供大脑(功能磁共振成像，fMRI)和行为(眨眼惊吓)负面情绪处理测量方面的培训，以启动应聘者的职业生涯，成为一名独立的临床神经学家，在焦虑情绪障碍的多层次、神经生物学、维度分析方面拥有专业知识。该提议包括三个组成部分：1)具有互补专业知识的导师团队；2)填补候选人先前教育空白的教学方法；3)对候选人的成长至关重要的实践经验。该研究计划测试维度跨诊断方法的有效性，将失调负面情绪处理的神经和行为测量与临床相关的焦虑负担联系起来，以共病负荷和自我报告的NA为特征。这项拟议项目的参与者将包括90名患有简单恐惧症(特定恐惧症或仅限于表现的社交焦虑)的成年人，他们被招募来填充3个共病负荷单元：1)n=30，没有共病；2)n=30，有1个其他焦虑或抑郁(AnxDep)障碍；3)n=30，有2个或更多其他AnxDep障碍，所有这些都与精神健康对照组(HCS，n=30)进行比较。K23利用了Mentor Phan由NIH资助的R01(MH101497[08/2013-07/2017])研究的招聘基础设施，但在实践上(不同的任务和扫描时段)和科学上是截然不同的。参与者将同时接受fMRI和肌电(EMG)惊吓记录：a)预期；b)对厌恶刺激的反应。与考生在fMRI情感神经科学、STARTER方法及其在与ADS相关的维度结构中的临床应用方面的培训目标一致，该项目的目标是：1)检验大脑的负面情绪加工测量、共病负荷与NA之间的关系；2)检验负面情绪加工的行为(START)测量与NA之间的关系；以及3)检验大脑与负面情绪加工的行为测量与共病负荷和NA的关系。共病负荷，疾病负担的标志，可能有助于理解维度和范畴的内在化精神病理学。通过完成这个项目和协调的培训计划，候选人将建立在她在事件相关电位(ERPs)和焦虑方面的先前专业知识的基础上，成为一名多模式的神经生物学专家，使用互补的分层方法(fMRI、ERPs、STARTLE)来弥合神经生物学和临床特征之间的差距，以改进诊断和指导新的治疗。

 DESCRIPTION (provided by applicant): Anxiety disorders (ADs) may be more similar than different in terms of neural dysfunction. Examining phenotypic variability that is independent of specific diagnoses may help explicate fundamental biobehavioral substrates of psychopathology in the ADs, leading to improved classification and treatment. For instance, comorbidity in the ADs is common and is known to relate to severity and measures of emotional reactivity such as self-reported negative affectivity (NA), yet evidence of its underlying neurobiology is scarce. The primary goal of this K23 is to provide the candidate with training in brain (functional magnetic resonance imaging, fMRI) and behavior (eyeblink startle) measures of negative emotion processing, in order to launch the candidate's career as an independent clinical neuroscientist with expertise in the multi-level, neurobiological, dimensional analysis of emotional dysfunction in anxiety. The proposal has three components: 1) a mentorship team with complementary expertise, 2) didactics to fill gaps in the candidate's previous education and 3) hands-on experience critical to the candidate's growth. The research plan tests the utility of a dimensional transdiagnostic approach in linking neural and behavioral measures of dysregulated negative emotion processing to clinically relevant anxiety burden characterized by comorbidity load and self-reported NA. Participants in the proposed project will comprise 90 adults with a 'simple' phobia (specific phobia or performance-only social anxiety) recruited to fill 3 comorbidity load cells: 1) n = 30 with no comorbidity; 2) n = 30 with 1 other anxiety or depressive (AnxDep) disorder; and 3) n = 30 with 2 or more other AnxDep disorders, all compared to psychiatrically healthy controls (HCs, n = 30). This K23 leverages the recruitment infrastructure of mentor Phan's NIH-funded R01 (MH101497 [08/2013-07/2017]) study, but is distinct practically (different tasks and scan sessions) and scientifically. Participants will undergo simultaneous fMRI and electromyographic (EMG) startle recording during: a) anticipation of; and b) response to aversive stimuli. Consonant with candidate's training goals in fMRI affective neuroscience, startle methodology and their clinical application to dimensional constructs relevant to ADs, the project's aims are to: 1) examine the relationship between brain measures of negative emotion processing, comorbidity load and NA; 2) examine the relationship between behavioral (startle) measures of negative emotion processing, comorbidity load and NA; and 3) examine the interrelationships between brain and behavioral measures of negative emotion processing in relation to comorbidity load and NA. Comorbidity load, a marker of disease burden, may aid understanding of dimensional and categorical internalizing psychopathology. Through completion of this project and the coordinated training plan, the candidate will build upon her prior expertise in event-related potentials (ERPs) and anxiety to emerge as a multi-modal, neurobiological expert using complementary, layered methodologies (fMRI, ERPs, startle) to close gaps between neurobiology and clinical profiles, in order to improve diagnosis and guide new treatments.